JP4573154B2 - A new crystalline form of cefdinir - Google Patents

Description

【００１４】
このスペクトルを、添付の図に示す。
【００１５】
新規な結晶形のセフジニルを、米国特許第４，９３５，５０７号で特許請求された結晶Ａと比較した加速安定度試験に付した。この試験から、この新規な結晶の安定度は少なくとも対照である結晶Ａの安定度に等しいことが明らかになった。０．０７ＮのＨＣｌ中での溶解度試験も実施し、それから新規な結晶の溶解度は結晶Ａの溶解度より低いことが明らかになった。しかし、溶解処理の所要時間を長くすると、新規な結晶形のセフジニルは、最初の１時間の後、結晶Ａより溶けやすかったという意味で状態が変化した。
【００１６】
結晶化の際にセフジニルの水溶液に加える有機溶媒は、酢酸エチルおよびテトラヒドロフランからなる群から選択することが好ましい。
【図面の簡単な説明】
【図１】新規な結晶形のセフジニルのＸ線回析スペクトルを示す図である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a novel crystalline form of cefdinir.
[0002]
[Prior art]
Cefdinir is a cephalosporin with high antibacterial activity and is described in US Pat. Nos. 4,559,334 and 4,585,860.
[0003]
U.S. Pat. No. 4,935,507 is obtained from a cefdinir solution prepared according to the teachings of the two aforementioned patents by crystallization by heating at ambient temperature or 40 ° C. in the pH range 1-4. Claimed is crystalline form A of cefdinir.
[0004]
Prior art documents related to the present invention include the following.
[Patent Document 1]
US Pat. No. 4,559,334 [Patent Document 2]
US Pat. No. 4,585,860 [Patent Document 3]
US Pat. No. 4,935,507
[Problems to be solved by the invention]
It is an object of the present invention to provide a new crystalline form of cefdinir that is less soluble than the known crystalline form of cefdinir.
[0006]
[Means for Solving the Problems]
The present invention relates to a dilute aqueous solution of cefdinir at a temperature between 0 ° C. and + 6 ° C. in the presence of at least one organic solvent whose total percentage (volume / volume in aqueous solution) does not exceed 10%. It relates to a new crystalline form of cefdinir which can be obtained at a pH between 5 and 3.
[0007]
The product obtained in this way has high stability and lower solubility than crystal A, but the final dissolved cefdinir amount can be higher than possible with crystal A. Such a feature can be very advantageous in clinical practice by allowing high concentrations to be obtained over time.
[0008]
DETAILED DESCRIPTION OF THE INVENTION
To clarify the understanding of the present invention, one aspect is described below by way of non-limiting examples.
[0009]
【Example】
Example 1
An aqueous solution at pH 5.5 containing 108.6 g of wet cefdinir (syn isomer obtained according to US Pat. No. 4,559,334) in 3000 ml of water is decolorized by stirring with carbon (10 g) for 30 minutes. . This is filtered, washed with 200 ml of water and diluted with ethyl acetate (300 ml). The solution is cooled to 0 ° C./+2° C. and quickly corrected to pH 2 by adding 6N HCl. Maintain under stirring at 0 ° C./+2° C. for 2 hours, filter and wash with deionized water. The product is dried at 25 ° C. under vacuum.
[0010]
Yield: 96 μg of yellow crystalline powder
K. F. : 6.0%
Titer: 949 ig / mg based on anhydrous base
Total impurities: 0.10%
[0011]
Using tetrahydrofuran (250 ml) in place of ethyl acetate, except that at a temperature of + 5 ° C., and treated in the same crystallization method, a result that can be superimposed with the result of the were obtained. The organic solvent can be formed from a mixture of organic solvents, the pH of the solution can be between 1.5 and 3, and the temperature can be between 0 ° C and + 6 ° C.
[0012]
The X-ray diffraction spectrum of the novel crystalline product obtained according to the above detailed example is as follows:
[0013]
[Table 2]

[0014]
This spectrum is shown in the accompanying figure.
[0015]
A new crystalline form of cefdinir was subjected to an accelerated stability test compared to crystal A claimed in US Pat. No. 4,935,507. This test revealed that the stability of this new crystal was at least equal to that of the control crystal A. A solubility test in 0.07N HCl was also performed, which revealed that the solubility of the new crystals was lower than that of crystal A. However, as the time required for the dissolution treatment was increased, the new crystalline form of cefdinir changed state in the sense that it was more soluble than crystal A after the first hour.
[0016]
The organic solvent added to the aqueous solution of cefdinir during crystallization is preferably selected from the group consisting of ethyl acetate and tetrahydrofuran.
[Brief description of the drawings]
FIG. 1 is an X-ray diffraction spectrum of a novel crystalline form of cefdinir.

Claims (3)

A crystalline form of cefdinir having an X-ray diffraction spectrum with the following characteristics:

To an aqueous solution of cefdinir, at least one organic solvent is added in a volume / volume percentage up to 10%, the solution is cooled to a temperature between 0 ° C. and + 6 ° C., and the pH is lowered to between 1.5 and 3. A method for obtaining a crystalline form of cefdinir according to claim 1, characterized in that a new cefdinir crystal is precipitated and isolated by a known technique. The process according to claim 2, wherein the organic solvent is selected from the group consisting of ethyl acetate and tetrahydrofuran used individually or mixed together.

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